OBJECTIVES: While interest in outcomes-based agreements has grown, their integration in value assessment is uncommon. We explored the impact of an outcomes-based agreement on the cost-effectiveness of cell and gene therapies using ICER’s review of Zynteglo for beta-thalassemia as a case example.

METHODS: A Markov cohort model with an upfront decision tree was used to model a hypothetical cohort of patients with transfusion dependent beta thalassemia being treated with Zynteglo or standard of care (SOC) over a lifetime time horizon. A publicly reported Federal Supply Schedule (FSS) price of $2.1 million was assumed for Zynteglo, and analyses were performed with and without an outcomes-based agreement involving an 80% payback if transfusion independence was not achieved or maintained over five years. Outcomes included life years, quality adjusted life years (QALY), costs, cost per QALY, and prices at $150,000/QALY with and without the outcomes-based agreement.

RESULTS: With an outcomes-based agreement, Zynteglo was more effective and more costly compared to SOC (incremental life years 2.85, QALYs 4.98, and costs $507,787) with an incremental cost-effectiveness ratio of $102,000/QALY. Under probabilistic analyses, Zynteglo had a 78% probability of being cost-effective at $150,000/QALY. With no outcomes-based agreement, incremental costs increased by 37% to $696,326, increasing the incremental cost-effectiveness ratio to $140,000/QALY. The probability of being cost-effectiveness declined to 54%. Under conservative assumptions of treatment benefit, uncertainties were better managed with an outcomes-based agreement in place. With an outcomes-based agreement in place, the price could rise to $2.4 million and remain cost-effective.

CONCLUSIONS: Direct integration of likely outcomes-based agreements in value assessments can allow stakeholders a full understanding of the cost and pricing implications of cell and gene therapies. Further exploration of the implications of such agreements is warranted, especially for interventions with greater uncertainty and/or safety concerns.